Tesis doctoral de Hugo Peluffo Zavala
Acute central nervous system (cns) damage consists of a multitude of inter-related and complex events, playing excitotoxicity, oxidative stress and inflammation important roles in the initial and secondary injury. In particular, the immature brain displays several characteristics that make it special in its reactions against acute injuries. In this context, this thesis contributes to the basic understanding of the oxidative stress and inflammation occurring after an nmda-mediated excitotoxic lesion to the immature brain, and to the development of neuroprotective gene therapy strategies for reducing immature brain damage by inhibiting oxidative stress. this thesis shows the in vivo expression and cell localization of one of the most important antioxidant proteins, cu/zn superoxide dismutase (sod), whose expression was observed mainly in neuronal cells, glia limitans and ependyma in the normal immature brain. However, after an excitotoxic lesion, the expression of this enzyme rapidly disappeared (at 4 hours) from the acutely affected neurons before they underwent cell death. One day after, expression of sod begun to increase in reactive astrocytes, present in the lesion for up to 7 days, the last time studied. Moreover, in the normal brain, the peroxynitrite product nitrotyrosine was observed in neurons and scattered astrocytes, however, after the excitotoxic lesion it was early increased in neurons of the lesion core, and after at 1 day post-lesion it increased also in astrocytes. Interestingly, the nitrated hypertrophied astrocytes from 3 days post-lesion onward represented a separated population of cells sharing several markers such as vimentin, metallothionein, sod, and high gfap content and hypertrophy, being always phenotypically the most reactive astrocytes. In addition, although being heavily nitrated and showing activated caspase 3 in their nuclei, nitrated astrocytes did not display any morphological sign of cell death nor tunel s
Datos académicos de la tesis doctoral «Neuroprotective gene therapy applied to the acutely damaged immature rat brain«
- Título de la tesis: Neuroprotective gene therapy applied to the acutely damaged immature rat brain
- Autor: Hugo Peluffo Zavala
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 18/05/2006
Dirección y tribunal
- Director de la tesis
- Bernardo Castellano López
- Tribunal
- Presidente del tribunal: josé Rodrigo
- gennadij Raivich (vocal)
- joan xavier Comella carnice (vocal)
- agustina García (vocal)